Comparative and quantitative ultrastructural studies of endocrine cells from the large bowel of European cat, beagle dog, and the monkey Callitrix jacchus were performed. The cat and monkey exhibited a roughly similar distribution of colonic endocrine cells with a frequency increasing toward the distal colon. On the contrary, the highest endocrine cell frequency in the dog colon was found in the cecum. In the dog and monkey, enterochromaffin (EC) cells were predominant in all segments. In the cat, non-EC cells were predominant in the proximal colon. For each colonic segment, relative percentages of EC and non-EC cells appeared on the whole to be roughly stable between individuals of the same species. Three subtypes of EC cells were distinguished in each species. Non-EC cells were characterized by large variation in size and electron densities of their granules: Mean granule size per cell extended from 210 to 850 nm in cat, 310 to 770 nm in dog, and 130 to 470 nm in monkey. In each species, statistical analyses indicated that the non-EC cell population was composed of two or more subpopulations. Some similarities were found between colonic endocrine cells of the monkey and man, whereas obvious differences appeared between the two carnivorous mammals. Immunocytochemical studies demonstrated the presence of cells containing enteroglucagon, somatostatin, or a pancreatic polypeptidelike substance in the colon of the monkey and the rectum of the three mammals. Correlative immunocytochemical and ultrastructural studies showed that the three kinds of immunostained endocrine non-EC cells in each species had rather round granules, with great electron densities. Some subpopulations, morphologically distinguished, did not react to any of the antisera used. This suggests either the existence of secretory cycle in some endocrine cells or, perhaps, the presence of peptides still unknown in this part of the gut.